Evaluation of the effects of clomipramine on canine thyroid function tests

To evaluate the effect of long-term clomipramine administration on the hypothalamic-pituitary-thyroid axis in healthy dogs, 14 healthy adult dogs were enrolled in a prospective study. Clomipramine (3 mg/kg PO q12h) was administered to all dogs beginning on day 0, and continued for 112 days. Serum total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), and thyroid-stimulating hormone (TSH) were measured on days 0, 7, 28, 42, 56, and 112. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Significant decreases were noted in serum T4, f4, and rT3 concentrations beginning on day 28 through the end of the study period. The lowest mean (+/-SEM) concentrations of T4 (26 +/- 1.2 to 17 +/- 0.5 nmol/L) and rT3 (1.21 +/- 0.13 to 0.83 +/- 0.08 nmol/L) occurred at day 112, whereas the lowest mean fT4 (29 +/- 2.4 to 18 +/- 1.7 pmol/L) was found on day 56 of clomipramine treatment. The effect of treatment over time on serum T3 concentration also was significant, but the deviation in T3 from baseline was variable. No significant effect of clomipramine treatment was noted on either pre- or post-TRH TSH concentrations. The 35 and 38% decreases in serum T4 and fT4 concentrations, respectively, during clomipramine administration may lead to a misdiagnosis of hypothyroidism. Although no evidence of hypothyroidism was noted in this study population, subclinical hypothyroidism may have occurred. A longer duration of treatment might further suppress thyroid function, and concurrent illness or other drug administration might exacerbate clomipramine's effects.     

Effect of non-steroidal aromatase inhibitor on blood plasma ovarian steroid and thyroid hormones in laying hen (Gallus domesticus)

HyLine Brown laying hens at 30 weeks of age were treated twice daily with Fadrozole, a non-steroidal aromatase inhibitor (AI; 1 mg/kg body weight; i.m.) for six consecutive days; control hens received saline. Blood was collected every day 0.5 h after oviposition, i.e. just before AI treatment. Ovarian steroids: progesterone (P4), testosterone (T) and estradiol (E2), and iodothyronines: thyroxine (T4), triiodothyronine (T3) and reverse-triiodothyronine (rT3) were measured in blood plasma by radioimmunoassay methods. In AI-treated hens a gradual delay in oviposition time was observed. AI significantly decreased P4 and E2 levels, maximally by 43% on day 4 and by 74% on day 5, respectively, and elevated T level, maximally by 248% on day 4. Simultaneously, the increases in T4 and T3 levels with no changes in rT3 levels were observed. The maximal effect of AI on T4 and T3 levels was found on day 4 (60% increase) and day 5 (312% increase), respectively. Moreover, statistically significant, negative coefficient of correlation between E2 and T3 (r = -0.51), and positive coefficient of correlation between T and T3 (r = 0.42) in AI-treated hens were found. The results obtained indicate that in mature laying hens there is a strong relationship between ovarian steroids and thyroid hormones, and suppression of E2 synthesis not only disrupts ovarian function but also affects the activity of the thyroid gland and peripheral metabolism of thyroid hormones.     

Relationships between thyroid status, tissue oxidative metabolism, and muscle differentiation in bovine fetuses

The temporal relationships between thyroid status and differentiation of liver, heart and different skeletal muscles were examined in 42 bovine fetuses from day 110 to day 260 of development using principal component analysis of the data. Plasma concentrations of reverse-triiodothyronine (rT(3)) and thyroxine (T(4)) increased during development from day 110 to day 210 or 260, respectively, whereas concentration of triiodothyronine (T(3)) and hepatic type-1 5'-deiodinase activity (5'D1) increased from day 180 onwards. On day 260, high T(4) and rT(3) and low T(3) concentrations were observed together with a mature 5'D1 activity. Cytochrome-c oxidase (COX) activity expressed per mg protein increased at day 180 in masseter and near birth in masseter, rectus abdominis and cutaneus trunci muscles (P<0.05). Significant changes in citrate synthase (CS) activity per mg protein were observed between day 110 and day 180 in the liver and between day 210 and day 260 in the liver, the heart and the longissimus thoracis muscle (P<0.05). Muscle contractile differentiation was shown by the disappearance of the fetal myosin heavy chain from day 180 onwards. A positive correlation (r>0.47, P<0.01) was shown between thyroid status parameters (5'D1, concentrations of T(4) and T(3)) and COX activity in muscles known to be oxidative after birth (masseter, rectus abdominis) but not in liver and heart, nor in muscles known to be glycolytic after birth (cutaneus trunci, longissimus thoracis). A similar correlation was found between thyroid parameters and CS activity in liver and masseter. Results indicate that elevation of plasma T(3) concentrations in the last gestational trimester could be involved in the differentiation of oxidative skeletal muscles.     

Endotoxn-induced nonthyroidal illness in dogs

OBJECTIVE: To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-alpha (TNF-alpha) activity in healthy dogs. ANIMALS: 6 healthy adult male dogs. PROCEDURES: Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-alpha activity were measured before (day-1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours. RESULTS: Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-alpha activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 andT3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs.     

Effects of propranolol on thyroid function in the dog

The effect of propranolol on thyroid function was evaluated in 6 mature euthyroid Beagles. Propranolol was administered orally in doses of 20 mg given 3 times daily for 2 weeks and then increased to 40 mg given 3 times daily for an additional 2 weeks. Six age- and sex-matched, euthyroid Beagles served as controls. Serum base-line concentrations of tetraiodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured before propranolol administration and at weekly intervals thereafter. Thyroid response to 5 IU of aqueous thyroid stimulating hormone administered IV was monitored before propranolol administration and at the 2- and 4-week treatment intervals. The T4, T3, and rT3 concentrations were measured by radioimmunoassay. There were no significant differences in base-line or postthyroid stimulating hormone serum concentrations of T4, T3, or rT3 in any individual or between the treatment or control groups at any treatment interval (P greater than 0.05). Seemingly, the therapeutic use of propranolol in euthyroid dogs should not alter thyroid hormone metabolism.     

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses

REASONS FOR PERFORMING STUDY: There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. OBJECTIVES: To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. METHODS: Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. RESULTS: Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. CONCLUSIONS: These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. POTENTIAL RELEVANCE: Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.     

Thyroid hormone balance in beluga whales, Delphinapterus leucas: dynamics after capture and influence of thyrotropin.

Ten beluga whales, Delphinapterus leucas, were captured in the Churchill River, Manitoba, held for up to five days, and then released. Blood samples were obtained immediately after capture and at 6-7 h intervals thereafter to monitor changes in circulating levels of thyroid hormones (TH). In six of the whales, total and free thyroxine (T4) and triiodothyronine (T3) declined steadily, whereas reverse-T3 (rT3) showed a transient increase during the first 24-36 h, followed by a decrease to below initial values. The changes in TH may have been due to glucocorticoid-mediated reduction in endogenous thyroid stimulating hormone (TSH), and inhibition of 5'-monodeiodinase in peripheral tissue. Two whales were given 10 IU of bovine TSH immediately after capture, and again one and two days later, resulting in successive increases in all TH, which remained elevated for at least 24 h after the last injection. Thereafter, circulating levels declined as in the untreated whales. Two whales receiving a single TSH injection on the fourth day responded with an increase in plasma TH comparable to that observed following the first TSH injection in the other two animals. Average (+/- SD) circulating level of rT3 at capture was 6.3 +/- 3.1 nmol/L, which is higher than reported for any other mammal and was significantly correlated with the naturally elevated levels of T4 that occur in belugas occupying estuaries during the summer.     

Thyroid hormone concentrations differ between donkeys and horses

Reasons for performing study: Reference intervals for thyroid hormones (TH) concentrations have not been previously established for donkeys, leading to potential misdiagnosis of thyroid disease. Objectives: To determine the normal values of TH in healthy adult donkeys and compare them to TH values from healthy adult horses. Methods: Thirty‐eight healthy Andalusian donkeys and 19 healthy Andalusian horses from 2 different farms were used. Donkeys were divided into 3 age groups: <5, 5–10 and >11 years and into 2 gender groups. Serum concentrations of fT3, tT3, rT3, fT4 and tT4 were quantified by radioimmunoassay. All blood samples were collected the same day in the morning. None of the animals had received any treatment for 30 days prior to sampling or had any history of disease. Both farms were in close proximity and under similar management. Differences between groups were determined using a one‐way ANOVA analysis followed by Fisher's LSD test. P<0.05 was considered significant. Results: Serum TH concentrations were higher in donkeys than in horses (P<0.01). Donkeys <5 years had higher serum rT3, fT4 and tT4 concentrations than donkeys >5 years (P<0.05). Furthermore, older donkeys (>11 years) had lower serum fT3 and tT3 concentrations than younger donkeys’ groups (<5 and 5–10 years, P<0.05). TH concentrations were not different between genders (fT3: P = 0.06; tT3: P = 0.08; rT3: P = 0.15; fT4: P = 0.89; and tT4: P = 0.19). Conclusions: Thyroid hormone concentrations are different between healthy adult donkeys and horses. Potential relevance: Establishing species‐specific TH reference ranges is important when evaluating clinicopathologic data in equids in order to avoid the misdiagnosis of thyroid gland dysfunction. Further studies to elucidate the physiological mechanisms leading to these differences are warranted.     

Immunohistochemical studies on the development of endocrine cells in the thyroid and parathyroid glands in the golden hamster

The development of endocrine cells in the thyroid and parathyroid glands in the golden hamster was studied immunohistochemically in relation to the formation of these glands. The thyroid was formed on day 9 of gestation by the ventral outpocketing of the foregut between the first and second branchial pouches. The thyroid epithelial cells were faintly thyroglobulin-immunoreactive on day 10.5 of gestation. This immunoreaction became intense thereafter, but was almost confined to the cytoplasm of epithelial cells until birth. It appeared in the follicular lumen in newborn animals. The ultimobranchial body was derived from the fifth pouch and fused with the thyroid on day 12 of gestation. Calcitonin-immunoreactive cells first appeared on day 14 of gestation in the dorsomedial part of the thyroid derived from the ultimobranchial body and increased in number and intensity thereafter. Somatostatin-immunoreactive cells also appeared in the dorsomedial part of the thyroid derived from the ultimobranchial body on day 13 of gestation, and increased in number in newborn animals, but decreased thereafter. The parathyroid was derived from the third pouch, situated on day 13 of gestation on the dorsolateral side of the thyroid, and surrounded by a common capsule with the thyroid. Parathormone-immunoreactive cells first appeared on day 15 of gestation in the parathyroid and increased in number and intensity after birth.     

Reverse 3,3',5'-triiodothyronine suppresses increase in free fatty acids in chickens elicited by dexamethasone or adrenaline

Reverse triiodothyronine (rT3) displays hypometabolic properties and antagonizes the hypermetabolic effect of 3,5,3'-triiodothyronine (T3). Previous experiments revealed that exogenous rT3 enhanced free fatty acids (FFA) in heat-stressed pullets and in chickens infected with lipopolysaccharide from Escherichia coli. To gain more data concerning the action of rT3, its effect on lipaemia produced by two main stress hormones: glucocorticoids and catecholamines, has been investigated. Synthetic glucocorticoid [dexamethasone (Dex)] and adrenaline (Adr) were used in two experiments. The experiments differed in duration, i.e. 24 h (Dex) or 150 min (Adr), and frequency of rT3 injections, i.e. two (Dex) or single (Adr) injections. The doses of hormones were as follows: rT3: 14 microg 100 g body weight/ injection (subcutaneously): Dex: 5 mg/animal (subcutaneously) and Adr: 1 mg/animal (intramuscularly). Maximal increases in FFA of 230.5 and 227.5% were noted after 1.5 and 3 h, respectively, in birds treated with Dex. Reverse T3 almost completely suppressed the rise of plasma FFA elicited by Dex. The increase in Dex + rT3-treated fowl was only 30.4% (not significant in comparison to control). Adr increased FFA by a maximum of 89.1 % and treatment with rT3 (Adr + rT3 group) suppressed this FFA increase to 42.5%. The data obtained demonstrate that rT3 suppresses lipaemia induced by an exogenous glucocorticoid and adrenaline. This suppression was more pronounced in glucocorticoid-treated birds, where Dex produced a higher lipolytic response than Adr.     

Electron paramagnetic resonance analysis of liver and serum in Sprague–Dawley rats exposed subchronically to coplanar pentachlorobiphenyl-congener 3,3',4,4',5

A unique electron paramagnetic resonance (EPR) signal was found at g  = 2.49 at 77 K in the liver tissues or microsomes of Sprague–Dawley rats that were exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126) or 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) by the oral route. This unique EPR signal was not detected in the liver excised from rats treated with carbon tetrachloride or 3-methyl-cholanthrene. The EPR signal intensity increased in proportion to the dose; no gender-specific difference was noted and the EPR signal at g  =   2.49 may have originated from heme-iron in cytochrome P450. Although, several serum parameters of the PCB126-treated rats were slightly higher than those of the control, PCB126 does not induce hepatic dysfunction at the dose range used in this study. 3,3',4,4',5-Pentachlorobiphenyl was given daily via the oral route to pregnant rats. The rats were reared until Day 22 of pregnancy, after which they were killed and EPR signals were obtained from the fetal livers. A signal at g  = 2.49 was observed for each fetal liver. These results indicate that the EPR signal at g  =   2.49 could be appropriate as a biomarker of exposure to PCB126 or TCDD in the situation where hepatic dysfunction is not detected.     

Thyroid hormones (TH) and 5'-monodeiodinase (5'-MD) activity in goat's milk from the early, mid- and late lactation period

The physiological significance of thyroid hormones (TH) present in colostrum and milk is still under consideration. The present study was aimed at determining milk thyroxine (T4) and triiodothyronine (T3) levels in three lactation phases (early, mid- and late) of the goat, and to measure activity of the milk 5'-deiodinase (5'-MD) enzyme responsible for the intramammary conversion of prohormone T4 to its metabolically highly active form T3. Thirty-two milk goats (Polish White breed) fed a standard diet were used for milk sampling. The highest TH levels in mammary secretion were recorded during the first 2-3 days post partum. Then the hormone levels decreased, and by about Day 7 fluctuated around the overall mean for the early-lactation phase (Days 1 to 24 of lactation), recording 0.134+/-0.059 microg T4 and 150.8+/-2.80 ng T3 in 100 ml of the milk. Such T4 concentrations appeared to be comparable to those in the rabbit and human, whereas the concentration of T3 was higher than in the cow, pig and mare's milk. Milk 5'-MD activity was higher (P < 0.01) during early and late lactation, compared to the mid-lactation phase. It coincided with low T4 and high T3 milk levels during early lactation, and with high milk T4 and low T3 concentrations during late lactation. The quantity of T4 and T3 available to newborn kids in milk suggests that TH ingested with the colostrum may have a physiological role during the early postnatal life of suckling goats.     

Thyroid function in dogs with spontaneous and induced congestive heart failure.

The effects of spontaneous and experimentally induced congestive heart failure on serum thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (reverse T3), free T4, free T3 concentrations, and the serum T4 and T3 concentrations in response to administration of thyrotropin were studied. Serum thyroid hormone concentrations were not different between eight dogs with spontaneous congestive heart failure and normal age matched control dogs. Seven dogs with experimental heart failure were tested before and after induction of congestive heart failure by rapid ventricular pacing. Mean serum T4 and free T3 concentrations were decreased and mean serum reverse T3 concentration was increased following induction of heart failure. The serum T4 and T3 responses to thyrotropin were not altered. Thyroid gland morphology appeared normal in dogs with experimental heart failure. Experimental congestive heart failure, similar to some other nonthyroidal illnesses, alters thyroid hormone secretion and metabolism in dogs.     

The effects of different iodide availabilities on thyroid function during development in Japanese quail

Japanese quail (Coturnix japonica) were used to study the effects of different egg iodide (I) availabilities on thyroid function during development. Low (less than 50 micrograms 1/kg feed in the maternal diet) and high (1200 micrograms 1/kg feed) I availability were compared to control levels (800 micrograms 1/kg feed), a standard supplementation for game bird feed. We measured thyroid gland content of I, triiodothyronine (T3) and thyroxine (T4), plasma concentrations of T3 and T4, hepatic 5' monodeiodinase (5'-D) activity, and the response of the thyroid gland to thyrotrophin (TSH) stimulation. Embryos, on day 14 of the 16.5-17 day incubation period, and 1-day chicks were used for most studies but thyroid gland hormone content and plasma hormone concentrations were determined for more stages. With high I, thyroidal I content was elevated but thyroidal T4 and T3 were not different from controls. Plasma T3 and T4, the thyroid gland response to TSH stimulation, and hepatic 5'-D activity did not differ between control and high I. Reduced body weight occurred with high I. In general, thyroid gland weight was not altered, but some high I birds exhibited thyroid hypertrophy and altered thyroid gland function. With low I availability, thyroid gland contents of I and T4 were reduced but thyroidal T3 content was maintained. The thyroid gland response to TSH stimulation, plasma thyroid hormone concentrations, and the developmental patterns of plasma thyroid hormones, hepatic 5'-D activity, body weight and thyroid weight were not different between control and low I groups. Developing Japanese quail exhibit excellent ability to adjust thyroid function over a wide range of I availabilities. Regulation appears to occur at the level of thyroid hormone synthesis in the thyroid gland, which allows most aspects of thyroid dynamics to remain unchanged in the maintenance of circulating thyroid hormone concentrations.     

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.     

Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism.

Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P less than 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P less than 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P less than 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ovarian iodide uptake and triiodothyronine generation in follicular fluid. The enigma of the thyroid ovary interaction

Since 1928, the iodine concentration in the ovary has been known to be higher than in every other organs except the thyroid. The ovarian iodide uptake varies with sexual activities, is enhanced by estrogens and a hypothyroid state and blocked by goitrogens. The recent discovery of a sodium iodide symporter (NIS) in ovaries has offered a possible mechanism for ovarian iodide uptake and other functional similarities to its thyroid counterpart. Nevertheless, the physiological significance of ovarian iodine uptake and accumulation remains unknown. The presence of thyroid hormones (TH) in follicular fluid (FF) has been established recently. Our preliminary studies on TH in FF (1996-1998) in rabbits, pigs, horses showed that the concentration of T4 is generally lower than that in serum and that for T3 is within the normal range or higher. A positive correlation exists between the T4 levels in FF and serum but not between the corresponding T3 levels. These studies revealed, for the first time, the presence of the ovarian 5'-monodeiodinase system in FF capable of generating T3 (ovary-born T3) by outer ring deiodination of T4. In mares, seasonal polyestrus, ovarian 5'-monodeiodinase (MD) activity and FF T3 levels have been found to be higher during the ovulatory period than in the anovulatory one. The exact physiological significance of this system generating T3 and coexisting with isoforms of TH receptors in granulosa cells has not been elucidated. A direct role of T3 for the early follicular development, differentiation and for the steroidogenic capability of granulosa cells, although strongly suggested by data obtained from in vitro studies, has to be elucidated.     

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares

OBJECTIVE: To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. RESULTS: Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.     

Evaluation of thyroid function in obese dogs and in dogs undergoing a weight loss protocol

Obesity and weight loss have been shown to alter thyroid hormone homeostasis in humans. In dogs, obesity is the most common nutritional problem encountered and weight loss is the cornerstone of its treatment. Therefore, it is important to clarify how obesity and weight loss can affect thyroid function test results in that species. The objectives of this study were to compare thyroid function in obese dogs and in lean dogs and to explore the effects of caloric restriction and weight loss on thyroid hormone serum concentrations in obese dogs. In the first experiment, 12 healthy lean beagles and 12 obese beagles were compared. Thyroid function was evaluated by measuring serum concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), thyrotropin (TSH), and reverse triiodothyronine (rT3) as well as a TSH stimulation test using 75 microg i.v. of recombinant human TSH. In the second experiment, eight obese beagles were fed an energy-restricted diet [average 63% maintenance energy requirement (MER)] until optimal weight was obtained. Blood samples for determination of TT4, FT4, TT3, TSH and rT3, were taken at the start and then weekly during weight loss. Only TT3 and TT4 serum concentrations were significantly higher in obese dogs as compared to lean dogs. In the second experiment, weight loss resulted in a significant decrease in TT3 and TSH serum concentrations. Thus obesity and energy restriction significantly alter thyroid homeostasis in dogs, but the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.